WO2023280309A1 - 一种三环四氢异喹啉类衍生物的盐型 - Google Patents
一种三环四氢异喹啉类衍生物的盐型 Download PDFInfo
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Abstract
Description
化合物编号 | IC 50(nM) |
1 | 0.69 |
化合物编号 | IC 50(nM) |
1 | 0.29 |
化合物编号 | IC 50(nM) |
1 | 1.36 |
实施例编号 | EC 50(nM) | Emax降解(%) |
氟维司群 | 0.06 | 100 |
1 | 0.38 | 107 |
化合物编号 | IC 50(μM) |
1 | 15.38 |
化合物编号 | IC 50(μM) |
1 | >30 |
化合物编号 | IC 50(μM) |
1 | >30 |
Claims (17)
- 根据权利要求1所述的式(I)所示化合物的药学上可接受的盐,其中式(I)所示化合物与酸分子的物质的量比选自5:1-1:5;优选1:1或1:3。
- 根据权利要求1-2任一项所述的式(I)所示化合物的药学上可接受的盐,其为磷酸盐,其中式(I)所示化合物与磷酸分子的物质的量比为1:3。
- 根据权利要求1-2任一项所述的式(I)所示化合物的药学上可接受的盐,其为硫酸盐,其中式(I)所示化合物与硫酸分子的物质的量比为1:1。
- 一种式(I)所示化合物的硫酸盐的A晶型,其中式(I)所示化合物与硫酸分子的物质的量比为1:1,以衍射角2θ角度表示的X-射线粉末衍射图谱,在6.6、7.9、15.1、20.7、22.1处有特征峰,优选地,以衍射角2θ角度表示的X-射线粉末衍射图谱,在6.6、7.9、13.4、14.5、15.1、19.3、19.8、20.7、22.1、24.8、25.4、25.7、27.6处有特征峰;最优选地,以衍射角2θ角度表示的X-射线粉末衍射图谱,在6.6、7.9、11.6、13.4、14.5、15.1、15.9、18.1、19.3、19.8、20.7、22.1、24.0、24.8、25.4、25.7、27.2、27.6、28.3、29.2处有特征峰。
- 根据权利要求4或6任一项所述的式(I)所示化合物的药学上可接受的盐的晶型,所述2θ角的误差范围为±0.2。
- 一种权利要求1-3任一项所述的式(I)所示化合物的药学上可接受的盐,所述药学上可接受的盐为磷酸盐,或权利要求4所述的式(I)所示化合物的磷酸盐的I晶型的制备方法,包括式(I)所示化合物与磷酸反应的步骤。
- 一种权利要求4所述的式(I)所示化合物的磷酸盐的I晶型的制备方法,包括以下步骤:1)配置式(I)所示化合物的溶剂A溶液,所述溶剂A选自酮类溶剂、酯类溶剂或醚类溶剂;优选丙酮、乙酸乙酯或甲基叔丁基醚;2)配置磷酸的溶剂B溶液,所述溶剂B选自水或醇类溶剂;优选甲醇、乙醇或水;3)混合式(I)所示化合物的溶剂A溶液与磷酸的溶剂B溶液后结晶析出。
- 一种权利要求1-2或5任一项所述的式(I)所示化合物的药学上可接受的盐,所述药学上可接受的盐为硫酸盐,或根据权利要求6所述的式(I)所示化合物的硫酸盐 的A晶型的制备方法,包括式(I)所示化合物与硫酸反应的步骤。
- 一种权利要求6所述的式(I)所示化合物的硫酸酸盐的A晶型的制备方法,包括以下步骤:1)配置式(I)所示化合物的溶剂A溶液,所述溶剂A选自酮类溶剂、酯类溶剂、腈类溶剂或醇类溶剂;所述溶剂A优选丙酮、乙酸乙酯、乙腈、甲醇或乙醇;2)配置硫酸的溶剂B溶液,所述溶剂B选自水、腈类溶剂或醇类溶剂;所述溶剂B优选甲醇、乙醇、水、乙腈;3)混合式(I)所示化合物的溶剂A溶液与硫酸的溶剂B溶液后结晶析出。
- 一种权利要求1所述的式(I)所示化合物的药学上可接受的盐的制备方法,包括式(I)所示化合物与酒石酸、柠檬酸、盐酸、氢溴酸、甲磺酸、甲酸、乙酸、琥珀酸、马来酸、苹果酸或对甲苯磺酸反应成盐的步骤。
- 一种药物组合物,包含以下成分:1)根据权利要求1-3、5任一项所述的式(I)所示化合物的药学上可接受的盐或根据权利要求4、6-7任一项所述的式(I)所示化合物的药学上可接受的盐的晶型,或其混合物;和2)任选自药学上可接受的载体、稀释剂或赋形剂。
- 一种药物组合物的制备方法,包括将1)根据权利要求1-3、5任一项所述的式(I)所示化合物的药学上可接受的盐或根据权利要求4、6-7任一项所述的式(I)所示化合物的药学上可接受的盐的晶型,或其混合物;和2)任选自药学上可接受的载体、稀释剂或赋形剂混合的步骤。
- 权利要求1-3、5任一项所述的式(I)所示化合物的药学上可接受的盐或根据权利要求4、6-7任一项所述的式(I)所示化合物的药学上可接受的盐的晶型,或其混合物,或权利要求13所述的药物组合物在制备雌激素受体调节剂中的用途;优选为在制备雌激素受体下调剂中的用途。
- 权利要求1-3、5任一项所述的式(I)所示化合物的药学上可接受的盐或根据权利要求4、6-7任一项所述的式(I)所示化合物的药学上可接受的盐的晶型,或其混合物,或权利要求13所述的药物组合物在制备预防和/或治疗癌症的药物中的用途,其中所述的癌症优选选自乳腺癌、子宫内膜癌、子宫癌、宫颈癌、皮肤癌、前列腺癌、卵巢癌、输 卵管肿瘤、血友病和白血病。
- 权利要求1-3、5任一项所述的式(I)所示化合物的药学上可接受的盐或根据权利要求4、6-7任一项所述的式(I)所示化合物的药学上可接受的盐的晶型,或其混合物,或权利要求13所述的药物组合物在制备预防和/或治疗雌激素受体介导的或依赖性的疾病或病症的药物中的用途;优选地,其中所述的雌激素受体介导的或依赖性的疾病或病症选自癌症、中枢神经系统缺陷、心血管系统缺陷、血液系统缺陷、免疫及炎症疾病、易感性感染、代谢缺陷、神经缺陷、精神缺陷和生殖缺陷;优选地,其中所述的癌症选自乳腺癌、子宫内膜癌、子宫癌、宫颈癌、皮肤癌、前列腺癌、卵巢癌、输卵管肿瘤、血友病和白血病;更优选,其中所述的癌症选自乳腺癌、卵巢癌、子宫内膜癌、前列腺癌和子宫癌。
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CA3225268A CA3225268A1 (en) | 2021-07-09 | 2022-07-08 | Salt types of tricyclic tetrahydro isoquinoline derivative |
EP22837054.0A EP4368624A1 (en) | 2021-07-09 | 2022-07-08 | Salt types of tricyclic tetrahydro isoquinoline derivative |
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2022
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- 2022-07-08 WO PCT/CN2022/104669 patent/WO2023280309A1/zh active Application Filing
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KR20240035515A (ko) | 2024-03-15 |
TW202317582A (zh) | 2023-05-01 |
AU2022307207A1 (en) | 2024-02-15 |
EP4368624A1 (en) | 2024-05-15 |
CA3225268A1 (en) | 2023-01-12 |
CN117642405A (zh) | 2024-03-01 |
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